Maternal peripheral lipoprotein-cholesterol and progesterone concentrations were determined from day 72 until day 100, in pregnant baboons (Papio sp) that were either untreated (n=4) or treated (n=3) with the inhibitor of hepatic lipoprotein production, 4-aminopyrazolo [3-4-d]pyrimidine (4-APP, 10 mg/kg BW) on days 98-99 of pregnancy (term=184 days). Although LDL-cholesterol and progesterone levels remained unchanged in untreated animals, LDL-cholesterol concentrations were nine-fold lower (p<0.005) in baboons receiving 4-APP. Progesterone levels were three and one-half fold lower (p<0.03) in 4-APP treated baboons than in untreated baboons. Reverse transcriptase-polymerase chain reaction was utilized to approximate relative changes in transcription of mRNAs for selected cholesterol-sensitive pathways in placental tissue collected on day 100. Thus, expression of mRNAs for LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reducase appeared enhanced, while acyl-coenzyme A:cholesterol acyl transferase (ACAT) mRNA was diminished in syncytiotrophoblast-enriched cell fractions, as a result of 4-APP administration. No relative differences in mRNAs were apparent in whole placental villous tissue, however, as a result of 4-APP treatment. This experiment demonstrates a significant decline in progesterone production elicited by maternal LDL-cholesterol withdrawal and demonstrates the efficacy of 4-APP administration during baboon pregnancy. Results also suggest a commensurate regulation of cholesterol-sensitive pathways in primate syncytiotrophoblast. However, no relative differences were apparent in mRNA levels for LDL receptor, HMG-CoA reductase and ACAT in whole placental villous tissue as a result of LDL-cholesterol withdrawal, which may suggest potential disparities in the mechanisms regulating cholesterol homeostasis in steroidgenically active syncytiotrophoblasts versus those in proliferative non-endocrine placental constituents.